DOE Human Subjects Resources

Adverse Events and Unanticipated Problems

Food and Drug Administration (FDA) regulations and the Common Rule require that adverse events be reported [45 CFR 46.103; 21 CFR 312.56(c),(d); 21 CFR 812.46(b)(1),(2)]. The Common Rule requires that any unanticipated problems involving risks to subjects or others be reported to the Institutional Review Board (IRB) of record (§745.103(5)), and FDA regulations contain requirements for the reporting of adverse events during all phases of product development as well as some post-approval reporting requirements [21 CFR 312.32(a) and 21 CFR 812.2(s)]. (Note that Chapter 14 of the Human Subjects Protection Resource Book provides an extensive discussion of IRB review of unanticipated problems or adverse events.)

It is important to recognize that:

  • most adverse events do not represent unanticipated problems involving risks to subjects or others, and,
  • not all unanticipated problems involving risks to subjects or others are adverse events.

However, it is most important that those events or problems representing unexpected serious harm to subjects be reported promptly to the IRB. The Office for Human Research Protections has issued comprehensive recommendations (including definitions and examples) on this subject: Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events.

Content reviewed: November 12, 2013